1. Field of the Invention
The present invention relates to novel sweetener blends of N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester (also known as neotame) and another sweetener.
2. Related Background Art N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester is a derivative of aspartame that has a sweetening potency that is about 40 times that of aspartame (and about 8,000 times that of sucrose). N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester may be prepared from aspartame as described in U.S. Pat. No. 5,480,668, U.S. Pat. No. 5,510,508, and U.S. Pat. No. 5,728,862, all of which are incorporated by reference herein.
These are four possible outcomes from sensory analysis of a blend of two physiologically active agents: suppression&lt;no synergy&lt;isobole synergy&lt;additive synergy. It is known that certain sweetener agents exhibit additive synergy when combined with each other. For example, U.S. Pat. No. 3,780,189 describes synergistic sweetener blends of aspartame and saccharin. However, isobole synergy in sweetener blends has not been previously recognized. Moreover, there is no disclosure or suggestion that N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester sweetener blends could be isobole synergistic.
The known additive synergy exhibited by aspartame sweetener blends is not a reasonable prediction of even additive synergy of neotame sweetener blends, let alone that such blends could be isobole synergistic. Structurally, N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester and aspartame differ in that, in N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester, a bulky neohexyl substituent is present on the amine nitrogen. ##STR1##
This structural difference results in dramatic differences in the physical and chemical properties of these compounds. For example, the melting point of N[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester is about 82.2.degree. C., while that of aspartame is 248.degree. C. In addition, N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester has much higher solubility in organic solvents than aspartame, and a much lower solubility in water. It is also known that N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester has a higher stability than aspartame under some pH conditions, as described in U.S. Pat. No. 5,480,688. The pronounced difference in sweetness potency between the two compounds is further evidence of their chemical dissimilarity.
Moreover, it is also known that a primary amino group such as the one on aspartame (pKa 7.7) generally has a different pKa than those from a secondary amino group such as the one on N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester (pKa 8.1). Moreover, the pKa's of an amino acid are known to have a profound impact on food applications (Labuza, T. P. and Basisier, M. W., 1992, "Physical Chemistry of Foods", H. G. Schwartzber and R. W. Hartel (Eds.), Marcel Dekker, Inc., New York). It is also well known that a secondary amine group can not form Schiff base type compounds with carbonyl compounds while a primary amine may. Furthermore, N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester exhibits physiologically different behavior than aspartame as exemplified by the dramatic difference in sweetness. These differences are clearly indicative that the characteristics and properties of one can not be said to suggest those of the other.
N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester may be used for sweetening a variety of products, including drinks, foods, confectionery, pastries, chewing gums, personal care, hygiene products and toiletries, as well as cosmetic, pharmaceutical and veterinary products. Its superior sweetening potency makes N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester an attractive alternative to aspartame because it permits the use of N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester in substantially smaller quantities than is required for aspartame to achieve an equivalent sweetening effect.
Synergy between two sweeteners can be defined as occurring when the sweetness intensity of a mixture of the sweeteners is greater than what would have been expected from their individual concentration response relationships. One explanation for the potential existence of synergy between sweeteners is the possibility of multiple sweetness receptor sites. Synergy is important in the use of sweeteners in food products because it offers both cost savings and flavor improvement possibilities. For example, a synergistic combination of aspartame and acesulfame-K is widely used to sweeten beverages in Europe. Fry, J., "Trends and Innovations in Low-Calorie Sweeteners", The World of Ingredients p. 16-18 (March/April 1998). Synergistic combinations are advantageous because they permit the use of smaller quantities of each of the individual agents than would be required otherwise. Thus, the use of synergistic combinations may offer a more cost effective way to achieve a desired physiological effect.
It would be highly desirable to provide synergistic blends of N-[N-(3,3-dimethylbutyl)-L-.alpha.-aspartyl]-L-phenylalanine 1-methyl ester with other sweeteners.